In vivo functional specificity and homeostasis of Drosophila 14-3-3 proteins
In vivo functional specificity and homeostasis of Drosophila 14-3-3 proteins
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DOI：
10.1534/genetics.107.072280
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发表时间：
2007-09-01
期刊：
影响因子：
3.3
通讯作者：
Skoulakis, Efthimios M. C.
中科院分区：
文献类型：
--
作者：
Acevedo, Summer F.;Tsigkari, K. Kirki;Skoulakis, Efthimios M. C.
普遍存在的14-3-3蛋白的功能特化或冗余是其生物学中的一个基本问题，源于它们高度保守的结构和多种共表达的同型。我们在体内利用两个果蝇14-3-3基因的突变来解决这个问题，这两个基因是莱昂纳多(14-33)和D14-3-3 epsilon。我们证明了D14-3-3 epsilon是胚胎孵化所必需的。然而，D14-3-3 epsilon缺失的纯合子存活下来，因为它们在孵化时上调了编码LEOII亚型的转录本，补偿了D14-3-3 epsilon的丢失。这一新的动态平衡反应解释了Drosopbila 14-3-3亚型的功能冗余和D14-3-3 epsilon突变体的存活。这种反应似乎是单向的，因为没有观察到LEO丢失时D14-3-3 epsilon的上调，并且LEO转录本的上调是阶段和组织特有的。相反，翼盘中的LEO水平没有改变，导致了具有D14-3-3 epsilon突变体特征的异常翼脉。然而，在翼盘中有条件地过度表达LEOI，而不是LEOII，可以部分挽救血管缺陷。因此，过量的特定LEO亚型可以在功能上补偿D14-3-3 epsilon的丢失，这是细胞特有的方式。这些结果表明，果蝇14-3-3蛋白之间以及体内两种LEO亚型之间的功能差异，可能是导致对14-3-3靶标的不同二聚体亲和力的基础。
The functional specialization or redundancy of the ubiquitous 14-3-3 proteins constitutes a fundamental question in their biology and stems from their highly conserved structure and multiplicity of coexpressed isotypes. We address this question in vivo using mutations in the two Drosophila 14-3-3 genes, leonardo (14-33) and D14-3-3 epsilon. We demonstrate that D14-3-3 epsilon is essential for embryonic hatching. Nevertheless, D14-3-3 epsilon null homozygotes survive because they upregulate transcripts encoding the LEOII isoform at the time of hatching, compensating D14-3-3 epsilon loss. This novel homeostatic response explains the reported functional redundancy of the Drosopbila 14-3-3 isotypes and survival of D14-3-3 epsilon mutants. The response appears unidirectional, as D14-3-3 epsilon elevation upon LEO loss was not observed and elevation of leo transcripts was stage and tissue specific. In contrast, LEO levels are not changed in the wing disks, resulting in the aberrant wing veins characterizing D14-3-3 epsilon mutants. Nevertheless, conditional overexpression of LEOI, but not of LEOII in the wing disk can partially rescue the venation deficits. Thus, excess of a particular LEO isoform can functionally compensate for D14-3-3 epsilon loss in a cellular-context-specific manner. These results demonstrate functional differences both among Drosophila 14-3-3 proteins and between the two LEO isoforms in vivo, which likely underlie differential dimer affinities toward 14-3-3 targets.